Direct observation of catch bonds involving cell-adhesion molecules

Abstract

Bonds between adhesion molecules are often mechanically stressed. A striking example is the tensile force applied to selectin–ligand bonds, which mediate the tethering and rolling of flowing leukocytes on vascular surfaces^1,2,3. It has been suggested that force could either shorten bond lifetimes, because work done by the force could lower the energy barrier between the bound and free states⁴ (‘slip’), or prolong bond lifetimes by deforming the molecules such that they lock more tightly^5,6 (‘catch’). Whereas slip bonds have been widely observed^{7,8,9,10,11,12,13,14}, catch bonds have not been demonstrated experimentally. Here, using atomic force microscopy and flow-chamber experiments, we show that increasing force first prolonged and then shortened the lifetimes of P-selectin complexes with P-selectin glycoprotein ligand-1, revealing both catch and slip bond behaviour. Transitions between catch and slip bonds might explain why leukocyte rolling on selectins first increases and then decreases as wall shear stress increases^9,15,16. This dual response to force provides a mechanism for regulating cell adhesion under conditions of variable mechanical stress.